Nerlynx (neratinib)

Combination therapy with neratinib and palbociclib demonstrated a favorable safety profile and clinical benefit rate in patients with HER-driven alterations. Pharmacokinetic analysis revealed a CYP3A4-mediated drug-drug interaction, leading to reduced clearance and increased plasma exposure of both agents, underscoring the importance of considering metabolic interactions in future clinical development.

Single-agent neratinib has limited activity in ERBB2-mutated lung cancers. Combinations with temsirolimus or trastuzumab did not markedly improve overall outcomes, producing durable responses in a limited subset of patients.

Lapatinib and neratinib are tyrosine kinase inhibitors (TKIs) approved for treating HER2-positive metastatic breast cancer, but their clinical use is limited by hepatotoxicity. This underscores the importance of targeting senescent cells or SASP factors to reduce liver toxicity and improve treatment outcomes, making the identification of effective senotherapeutics a vital research focus. There hasn't been any literature report demonstrating the effect of TKI-induced liver cell secretome on macrophage polarization.

P=N/A, N=80, Not yet recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

P1, N=18, Recruiting, Fox Chase Cancer Center | Trial primary completion date: Jun 2025 --> Jun 2026

These results provide additional data supporting the safety and exploratory effectiveness of neratinib in the EAP, reflecting real-world clinical practice.

Additionally, we identified four potential drug targets, including PFAS, EIF2S3, EIF6, and NFKB2. Molecular docking analysis suggested that neratinib, a clinically approved drug, could serve as a promising therapeutic agent for GSRCC, offering new avenues for clinical intervention.

These findings underscore the therapeutic potential and suitability of these nanoplatforms for the precise and controlled targeting of HER2-positive tumors. This study is the first to synchronize the delivery of multiple agents-docetaxel, neratinib, and trastuzumab-within a nanoparticle system for treating HER2-positive tumors, offering a promising strategy to enhance treatment outcomes for HER2 positive breast cancer patients.

Furthermore, combination anti-EGFL6 therapy with the pan-EGFR receptor inhibitor neratinib, compared to either therapy alone, led to an increase in aberrant pERK localization and cancer cell death in vitro and significant restricted tumor growth in vivo...We also reveal a novel function of pERK downstream of pHER3 at the centrosome in mitosis. Importantly, we show that EGFL6 is an important therapeutic target to enhance the efficacy of EGFR/HER-targeted therapy.

P2, N=460, Recruiting, Patrick Wen, MD | Trial completion date: Apr 2027 --> Apr 2028 | Trial primary completion date: Feb 2027 --> Feb 2028

Biomarker analysis uncovered interesting new hypothesis-generating data warranting future study in IBC. ClinicalTrials.gov NCT03101748.

P2, N=30, Recruiting, Ruth O'Regan | Trial completion date: Oct 2025 --> Jan 2026 | Trial primary completion date: Sep 2025 --> Dec 2025